Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from Kwazulu-Natal, South Africa: Implications for vaccine and antiretroviral control strategies

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dc.contributor.authorGordon M.
dc.contributor.authorDe Oliveira T.
dc.contributor.authorBishop K.
dc.contributor.authorCoovadia H.M.
dc.contributor.authorMadurai L.
dc.contributor.authorEngelbrecht S.
dc.contributor.authorVan Rensburg E.J.
dc.contributor.authorMosam A.
dc.contributor.authorSmith A.
dc.contributor.authorCassol S.
dc.date.accessioned2011-05-15T16:17:17Z
dc.date.available2011-05-15T16:17:17Z
dc.date.issued2003
dc.description.abstractThe KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naive patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.
dc.description.versionArticle
dc.identifier.citationJournal of Virology
dc.identifier.citation77
dc.identifier.citation4
dc.identifier.issn0022538X
dc.identifier.other10.1128/JVI.77.4.2587-2599.2003
dc.identifier.urihttp://hdl.handle.net/10019.1/14153
dc.subjectantiretrovirus agent
dc.subjectepitope
dc.subjectHuman immunodeficiency virus vaccine
dc.subjectnucleoside
dc.subjectnucleotide
dc.subjectprotein kinase C
dc.subjectproteinase
dc.subjectRNA directed DNA polymerase
dc.subjectRNA directed DNA polymerase inhibitor
dc.subjectadult
dc.subjectamino acid sequence
dc.subjectarticle
dc.subjectcodon
dc.subjectcontrolled study
dc.subjectcorrelation analysis
dc.subjectcytotoxic T lymphocyte
dc.subjectdrug binding site
dc.subjectdrug efficacy
dc.subjectdrug sensitivity
dc.subjectenzyme active site
dc.subjectenzyme phosphorylation
dc.subjectepidemic
dc.subjectethnic group
dc.subjectfemale
dc.subjectgene disruption
dc.subjectgene mutation
dc.subjectgenetic analysis
dc.subjectgenetic polymorphism
dc.subjectgenetic variability
dc.subjectglycosylation
dc.subjecthelper cell
dc.subjecthuman
dc.subjectHuman immunodeficiency virus 1
dc.subjectinfection control
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectnucleotide sequence
dc.subjectphylogeny
dc.subjectpolymorphic locus
dc.subjectpreschool child
dc.subjectpriority journal
dc.subjectprotein motif
dc.subjectretrospective study
dc.subjectSouth Africa
dc.subjectvirus envelope
dc.subjectvirus resistance
dc.subjectvirus typing
dc.subjectAdult
dc.subjectAIDS Vaccines
dc.subjectAmino Acid Sequence
dc.subjectAmino Acid Substitution
dc.subjectAnti-HIV Agents
dc.subjectDrug Resistance, Viral
dc.subjectFemale
dc.subjectGenes, env
dc.subjectHIV Infections
dc.subjectHIV Protease
dc.subjectHIV-1
dc.subjectHIV-1 Reverse Transcriptase
dc.subjectHumans
dc.subjectInfant
dc.subjectMale
dc.subjectMolecular Sequence Data
dc.subjectPhylogeny
dc.subjectSequence Analysis, DNA
dc.subjectSouth Africa
dc.subjectVariation (Genetics)
dc.titleMolecular characteristics of human immunodeficiency virus type 1 subtype C viruses from Kwazulu-Natal, South Africa: Implications for vaccine and antiretroviral control strategies
dc.typeArticle
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